Ketone body metabolism US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Ketone body metabolism. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Ketone body metabolism US Medical PG Question 1: A 45-year-old man is brought to the emergency department by ambulance after vomiting blood. The patient reports that he only ate a small snack the morning before and had not eaten anything for over 24 hours. At the hospital, the patient is stabilized. He is admitted to a surgical floor and placed on NPO with a nasogastric tube set to intermittent suction. He has been previously diagnosed with liver cirrhosis. An esophagogastroduodenoscopy (EGD) has been planned for the next afternoon. At the time of endoscopy, some pathways were generating glucose to maintain serum glucose levels. Which of the following enzymes catalyzes the irreversible biochemical reaction of this process?
- A. Glucose-6-phosphate dehydrogenase
- B. Glycogen phosphorylase
- C. Enolase
- D. Glyceraldehyde-3-phosphate dehydrogenase
- E. Fructose-1,6-bisphosphatase (Correct Answer)
Ketone body metabolism Explanation: ***Fructose-1,6-bisphosphatase***
- The scenario describes a patient in a fasting state for over 24 hours, during which **gluconeogenesis** is crucial for maintaining blood glucose levels.
- **Fructose-1,6-bisphosphatase** is one of the key regulatory enzymes in gluconeogenesis, catalyzing an **irreversible reaction** that bypasses the phosphofructokinase-1 step of glycolysis.
*Glucose-6-phosphate dehydrogenase*
- This enzyme is involved in the **pentose phosphate pathway**, which generates NADPH and precursors for nucleotide synthesis.
- It does not directly participate in gluconeogenesis to produce glucose from non-carbohydrate sources.
*Glycogen phosphorylase*
- This enzyme is involved in **glycogenolysis**, the breakdown of glycogen into glucose-1-phosphate.
- While it releases glucose, the body's glycogen stores would likely be depleted after over 24 hours of fasting, making gluconeogenesis the primary pathway for glucose production.
*Enolase*
- Enolase is an enzyme in the glycolytic pathway, catalyzing the reversible conversion of 2-phosphoglycerate to phosphoenolpyruvate.
- It is not an enzyme of gluconeogenesis, nor does it catalyze an irreversible step in the glucose production process during fasting.
*Glyceraldehyde-3-phosphate dehydrogenase*
- This enzyme is also part of glycolysis, catalyzing the reversible oxidation and phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate.
- Like enolase, it is not an irreversible enzyme in gluconeogenesis that would be generating glucose under fasting conditions.
Ketone body metabolism US Medical PG Question 2: A 30-year-old woman is brought to the emergency department by ambulance after being found unconscious in her bedroom by her roommate. The roommate says the patient has type 1 diabetes and takes her insulin regularly. Her pulse is 110/min, the respiratory rate is 24/min, the temperature is 36.6°C (97.9°F), and the blood pressure is 95/65 mm Hg. She is breathing heavily and gives irrelevant responses to questions. Her skin and mucous membranes appear dry. Her breath has a fruity smell to it. Tendon reflexes are slightly delayed. The laboratory findings include:
Finger-stick glucose 530 mg/dL
Arterial blood gas analysis
pH 7.1
pO2 94 mm Hg
pCO2 32 mm Hg
HCO3 17 mEq/L
Serum
Sodium 136 mEq/L
Potassium 3.2 mEq/L
Chloride 136 mEq/L
Blood urea nitrogen 20 mg/dL
Serum creatinine 1.2 mg/dL
Urine examination
Glucose positive
Ketones positive
Leucocytes negative
Nitrite negative
RBC negative
Casts negative
Which of the following abnormalities accounts for her sweet smelling breath?
- A. Diminished glucose metabolism
- B. Fermentation of excess blood sugars
- C. Extrahepatic ketone production
- D. Inhibition of HMG-CoA synthase
- E. Excessive mobilization of fatty acids (Correct Answer)
Ketone body metabolism Explanation: ***Excessive mobilization of fatty acids***
- The fruity smell on the breath is due to the presence of **acetone**, a ketone body. Acetone is produced from the excessive breakdown of **fatty acids** into acetyl-CoA, which then enters ketogenesis
- This process is triggered by **insulin deficiency** and high glucagon levels, leading the body to use fat as its primary energy source instead of glucose.
*Diminished glucose metabolism*
- While diminished glucose metabolism is a core problem in **diabetic ketoacidosis (DKA)**, it directly leads to the body's reliance on **fatty acid oxidation**, which then produces ketones.
- The sweet smell itself is a result of the **ketone bodies**, specifically acetone, rather than the diminished glucose metabolism directly.
*Fermentation of excess blood sugars*
- **Fermentation** of sugars typically occurs in anaerobic conditions, often involving microorganisms, and produces products like lactic acid or alcohol, not ketones.
- The fruity breath in DKA is due to **ketone body production**, not fermentation of glucose.
*Extrahepatic ketone production*
- **Ketone bodies** (acetoacetate, β-hydroxybutyrate, and acetone) are primarily produced in the **liver** (hepatic), not extrahepatically.
- The liver is the main site for **ketogenesis** when fatty acid oxidation is elevated.
*Inhibition of HMG-CoA synthase*
- **HMG-CoA synthase** is a crucial enzyme in the **biosynthesis of ketone bodies** in the liver.
- **Inhibition** of this enzyme would *decrease* ketone body production, rather than cause the sweet-smelling breath associated with their excess.
Ketone body metabolism US Medical PG Question 3: A 65-year-old male prisoner goes on a hunger strike to protest the conditions of his detainment. After 5 days without food, he suffers a seizure for which he is taken into a medical facility. On physical examination, he looks pale and diaphoretic. His blood glucose level is 50 mg/dL. In order to keep a constant supply of energy to his brain, which of the following molecules is his liver releasing into the bloodstream?
- A. Glycogen
- B. Glucose-6-phosphate
- C. ß-hydroxybutyric acid (Correct Answer)
- D. Fatty acids
- E. Glucose-1-phosphate
Ketone body metabolism Explanation: ***ß-hydroxybutyric acid***
- After 5 days of a hunger strike, **glycogen stores** are depleted, forcing the body to rely on **fatty acid oxidation** and **ketone body production** in the liver as an alternative fuel source for the brain.
- **ß-hydroxybutyrate** is one of the primary ketone bodies released by the liver into the bloodstream to provide energy, especially for the brain, during prolonged fasting.
*Glycogen*
- **Glycogenolysis** (breakdown of glycogen) is a short-term response to low blood glucose and supplies glucose for only about 24-36 hours of fasting. After 5 days, **hepatic glycogen stores** would be largely depleted.
- The liver releases **free glucose** into the bloodstream, not intact glycogen, from glycogen breakdown.
*Glucose-6-phosphate*
- **Glucose-6-phosphate** is an intermediate in glycolysis and gluconeogenesis, but it is not directly released into the bloodstream by the liver.
- It must be converted to **free glucose** by glucose-6-phosphatase before it can exit the hepatocyte and enter circulation.
*Fatty acids*
- The liver takes up **fatty acids** from adipose tissue breakdown during prolonged fasting to convert them into **ketone bodies**.
- While fatty acids are a major energy source for other tissues, the **brain cannot directly utilize fatty acids** for energy due to the inability of long-chain fatty acids to cross the blood-brain barrier.
*Glucose-1-phosphate*
- **Glucose-1-phosphate** is an intermediate formed during the breakdown of glycogen (glycogenolysis).
- Like glucose-6-phosphate, it is not directly released into the bloodstream but is further metabolized within the hepatocyte, eventually leading to the release of **free glucose**.
Ketone body metabolism US Medical PG Question 4: Researchers are experimenting with hormone levels in mice in fasting and fed states. To test hormone levels in the fed state, the mice are given an oral glucose load and various hormones are measured in a blood sample. Researchers are most interested in the hormone whose blood levels track evenly with C-peptide levels. The hormone the researchers are most interested in is responsible for which of the following actions in the body?
- A. Protein catabolism
- B. Fatty acid breakdown
- C. Fatty acid synthesis (Correct Answer)
- D. Ketogenesis
- E. Lipolysis
Ketone body metabolism Explanation: ***Fatty acid synthesis***
- The hormone whose blood levels track evenly with **C-peptide** levels after a glucose load is **insulin**.
- Insulin is a key anabolic hormone that promotes **fatty acid synthesis** from excess glucose in the fed state, particularly in the liver and adipose tissue.
*Protein catabolism*
- **Insulin** is an anabolic hormone that generally **inhibits protein catabolism** and promotes protein synthesis.
- Conditions like **glucagon excess** or **cortisol excess** promote protein catabolism, not insulin.
*Fatty acid breakdown*
- **Insulin inhibits fatty acid breakdown** (beta-oxidation) by suppressing hormone-sensitive lipase.
- **Glucagon** and **epinephrine** promote fatty acid breakdown, especially during fasting.
*Ketogenesis*
- **Insulin inhibits ketogenesis** by reducing the supply of fatty acids to the liver and inhibiting the enzymes involved in ketone body formation.
- **Glucagon** and **low insulin levels** (as in uncontrolled diabetes or prolonged fasting) promote ketogenesis.
*Lipolysis*
- **Insulin is a potent inhibitor of lipolysis** (breakdown of triglycerides into fatty acids and glycerol) in adipose tissue.
- **Glucagon**, **catecholamines**, and **growth hormone** stimulate lipolysis.
Ketone body metabolism US Medical PG Question 5: An 11-year-old boy is brought to the emergency department because he was found to have severe abdominal pain and vomiting in school. On presentation, he is found to be lethargic and difficult to arouse. His parents noticed that he was eating and drinking more over the last month; however, they attributed the changes to entering a growth spurt. Physical exam reveals deep and rapid breathing as well as a fruity odor on his breath. Which of the following sets of labs would most likely be seen in this patient?
- A. Glucose: 90 mg/dL, pH: 7.4, Bicarbonate: 24 mEq/L
- B. Glucose: 300 mg/dL, pH: 7.4, Bicarbonate: 24 mEq/L
- C. Glucose: 90 mg/dL, pH: 7.2, Bicarbonate: 10 mEq/L
- D. Glucose: 300 mg/dL, pH: 7.4, Bicarbonate: 10 mEq/L
- E. Glucose: 300 mg/dL, pH: 7.2, Bicarbonate: 10 mEq/L (Correct Answer)
Ketone body metabolism Explanation: ***Glucose: 300 mg/dL, pH: 7.2, Bicarbonate: 10 mEq/L***
- The patient's symptoms (polydipsia, polyphagia, lethargy, abdominal pain, vomiting, deep and rapid breathing, fruity breath) are classic for **Diabetic Ketoacidosis (DKA)**, which involves **hyperglycemia**, **metabolic acidosis** (low pH and bicarbonate), and **ketone production**.
- A glucose level of 300 mg/dL indicates significant hyperglycemia, a pH of 7.2 shows acidosis, and a bicarbonate of 10 mEq/L confirms the metabolic component of DKA.
*Glucose: 90 mg/dL, pH: 7.4, Bicarbonate: 24 mEq/L*
- These values represent normal glucose, pH, and bicarbonate levels, which are entirely inconsistent with the patient's severe symptoms of **DKA** and metabolic derangement.
- A glucose of 90 mg/dL is within the normal range, and a pH of 7.4 with a bicarbonate of 24 mEq/L indicates a normal acid-base balance.
*Glucose: 300 mg/dL, pH: 7.4, Bicarbonate: 24 mEq/L*
- While a glucose of 300 mg/dL indicates hyperglycemia, the normal pH and bicarbonate levels (7.4 and 24 mEq/L respectively) do not align with the **metabolic acidosis** characteristic of DKA.
- The patient's presentation with **Kussmaul breathing** and fruity breath are strong indicators of acidosis, which is absent in these lab values.
*Glucose: 90 mg/dL, pH: 7.2, Bicarbonate: 10 mEq/L*
- Although the low pH and bicarbonate suggest **metabolic acidosis**, the normal glucose level of 90 mg/dL rules out **hyperglycemia**, which is a prerequisite for a diagnosis of DKA.
- The combination of severe acidosis and normal glucose is indicative of other causes of metabolic acidosis, but not DKA.
*Glucose: 300 mg/dL, pH: 7.4, Bicarbonate: 10 mEq/L*
- This set of labs shows hyperglycemia (glucose 300 mg/dL) and low bicarbonate, but the **normal pH (7.4)** is inconsistent with the severe metabolic acidosis expected in DKA, especially given the patient's symptoms like Kussmaul breathing.
- A patient with significant bicarbonate depletion (10 mEq/L) due to DKA would typically have a significantly lower, acidotic pH.
Ketone body metabolism US Medical PG Question 6: The balance between glycolysis and gluconeogenesis is regulated at several steps, and accumulation of one or more products/chemicals can either promote or inhibit one or more enzymes in either pathway. Which of the following molecules if increased in concentration can promote gluconeogenesis?
- A. ADP
- B. Acetyl-CoA (Correct Answer)
- C. AMP
- D. Fructose-2,6-bisphosphate
- E. Insulin
Ketone body metabolism Explanation: ***Acetyl-CoA***
- **Acetyl-CoA** promotes gluconeogenesis by activating **pyruvate carboxylase**, the enzyme that converts pyruvate to oxaloacetate, effectively pushing the pathway forward.
- High levels of **Acetyl-CoA** generally signal a state of abundant energy from fatty acid oxidation, indicating that glucose is not immediately needed for energy and can be synthesized for storage or use elsewhere.
*ADP*
- **ADP** is a key indicator of low cellular energy and **stimulates** glycolysis while **inhibiting** gluconeogenesis to produce ATP.
- Its presence signals a need for energy synthesis rather than glucose production.
*AMP*
- **AMP** also signals low energy status and is a powerful **allosteric activator** of **phosphofructokinase-1 (PFK-1)**, the rate-limiting enzyme in glycolysis.
- Activates **AMP-activated protein kinase (AMPK)**, which promotes catabolic processes like glycolysis and inhibits anabolic processes like gluconeogenesis.
*Fructose-2,6-bisphosphate*
- **Fructose-2,6-bisphosphate** is a potent **allosteric activator** of **PFK-1** in glycolysis and a strong **inhibitor** of **fructose-1,6-bisphosphatase** in gluconeogenesis.
- Its levels increase in response to insulin, promoting glucose utilization and inhibiting glucose production.
*Insulin*
- **Insulin** is a hormone that **promotes glucose uptake** and utilization by tissues and **inhibits gluconeogenesis**.
- It achieves this by activating enzymes involved in glycolysis and glycogen synthesis while inhibiting key enzymes in gluconeogenesis, such as **fructose-1,6-bisphosphatase**.
Ketone body metabolism US Medical PG Question 7: A 35-year-old man comes to the physician because of fatigue and generalized weakness for the past year. He has noticed he has been having fewer bowel movements. He has had pain with defecation and small amounts of blood when wiping. He has not lost weight despite increased efforts to diet and exercise. He has had no fever, throat pain, or difficulty swallowing. His temperature is 36.5°C (97.7°F), pulse is 50/min, blood pressure is 120/90 mm Hg, and BMI is 35 kg/m2. Physical examination shows dry skin and a distended abdomen. There is 1+ pitting edema in the lower extremities. On neurological examination, deep tendon reflexes are 1+. Further evaluation of this patient is most likely to show which of the following findings?
- A. Hyperglycemia
- B. Decreased serum creatinine
- C. Elevated serum low-density lipoprotein (Correct Answer)
- D. Decreased plasma homocysteine concentrations
- E. Decreased serum creatine kinase
Ketone body metabolism Explanation: ***Elevated serum low-density lipoprotein***
- The patient's symptoms (fatigue, generalized weakness, constipation, weight gain despite efforts, cold intolerance implied by dry skin, bradycardia, and edema) are highly suggestive of **hypothyroidism**.
- **Hypothyroidism** classically leads to **hyperlipidemia**, specifically elevated **LDL cholesterol**, due to decreased catabolism of cholesterol.
*Decreased serum creatine kinase*
- **Hypothyroidism** typically causes **myopathy**, which can manifest as elevated, not decreased, serum **creatine kinase** levels.
- Muscle weakness and fatigue in hypothyroidism are often associated with muscle damage and elevated CK.
*Hyperglycemia*
- While hypothyroidism can impact glucose metabolism, it more commonly leads to **insulin resistance** and can contribute to **hyperglycemia**, but it is not a direct or consistent consequence, and other factors are often more significant.
- However, hypothyroidism is not primarily characterized by hyperglycemia as a direct pathognomonic finding.
*Decreased serum creatinine*
- **Hypothyroidism** is typically associated with **decreased glomerular filtration rate (GFR)**, which can lead to **increased serum creatinine**, not decreased.
- A decreased GFR would imply reduced clearance of creatinine, thus elevating its serum concentration.
*Decreased plasma homocysteine concentrations*
- **Hypothyroidism** is linked to **elevated plasma homocysteine** concentrations, likely due to impaired metabolism (e.g., reduced activity of methionine synthase).
- High homocysteine levels are a risk factor for cardiovascular disease.
Ketone body metabolism US Medical PG Question 8: A 9-month-old girl is brought to the physician because of a 1-month history of poor feeding and irritability. She is at the 15th percentile for height and 5th percentile for weight. Examination shows hypotonia and wasting of skeletal muscles. Cardiopulmonary examination shows no abnormalities. There is hepatomegaly. Her serum glucose is 61 mg/dL, creatinine kinase is 100 U/L, and lactic acid is within the reference range. Urine ketone bodies are elevated. Which of the following enzymes is most likely deficient in this patient?
- A. Glucose-6-phosphatase
- B. Muscle phosphorylase
- C. Acid alpha-glucosidase
- D. Glycogen debrancher (Correct Answer)
- E. Glucocerebrosidase
Ketone body metabolism Explanation: ***Glycogen debrancher***
- The patient's symptoms of **hepatomegaly**, **hypoglycemia**, **poor feeding**, **growth failure**, and **elevated urine ketones** in the presence of normal lactic acid suggest Type III glycogen storage disease (Cori disease), caused by a deficiency in **glycogen debrancher enzyme**.
- **Muscle wasting** and **hypotonia** are also consistent with Type III GSD, as the debranching enzyme is present in both liver and muscle.
*Glucose-6-phosphatase*
- Deficiency in **glucose-6-phosphatase** (Type I GSD, Von Gierke disease) also presents with **hepatomegaly** and **hypoglycemia**.
- However, Type I GSD is characterized by **lactic acidosis**, which is explicitly stated as normal in this patient, and **hyperlipidemia**, which is not mentioned.
*Muscle phosphorylase*
- Deficiency in **muscle phosphorylase** (Type V GSD, McArdle disease) primarily affects skeletal muscle, causing **exercise intolerance** and **muscle pain**.
- It does not typically present with **hypoglycemia**, **hepatomegaly**, or **growth failure** in infancy.
*Acid alpha-glucosidase*
- Deficiency in **acid alpha-glucosidase** (Type II GSD, Pompe disease) causes accumulation of glycogen in lysosomes, leading to severe **cardiomyopathy**, **hypotonia**, and **muscle weakness**.
- While hypotonia is present, the absence of **cardiomegaly** and significant **liver involvement** makes this diagnosis less likely.
*Glucocerebrosidase*
- Deficiency in **glucocerebrosidase** causes Gaucher disease, a lysosomal storage disorder, not a glycogen storage disorder.
- Symptoms include **hepatosplenomegaly**, **bone crises**, and neurological symptoms, but not **hypoglycemia** or isolated muscle wasting directly related to glycogen metabolism.
Ketone body metabolism US Medical PG Question 9: A 27-year-old man presents to the emergency department with his family because of abdominal pain, excessive urination, and drowsiness since the day before. He has had type 1 diabetes mellitus for 2 years. He ran out of insulin 2 days ago. The vital signs at admission include: temperature 36.8°C (98.2°F), blood pressure 102/69 mm Hg, and pulse 121/min. On physical examination, he is lethargic and his breathing is rapid and deep. There is a mild generalized abdominal tenderness without rebound tenderness or guarding. His serum glucose is 480 mg/dL. Arterial blood gas of this patient will most likely show which of the following?
- A. ↑ pH, ↑ bicarbonate, and normal pCO2
- B. ↓ pH, ↓ bicarbonate and ↑ anion gap (Correct Answer)
- C. ↑ pH, normal bicarbonate and ↓ pCO2
- D. ↓ pH, ↓ bicarbonate and normal anion gap
- E. ↓ pH, normal bicarbonate and ↑ pCO2
Ketone body metabolism Explanation: ***↓ pH, ↓ bicarbonate and ↑ anion gap***
- The patient's symptoms (abdominal pain, excessive urination, drowsiness, rapid and deep breathing, hyperglycemia) and history of Type 1 diabetes with missed insulin are highly suggestive of **diabetic ketoacidosis (DKA)**.
- DKA is characterized by **metabolic acidosis** due to the accumulation of ketone bodies, leading to a **decreased pH**, consumption of bicarbonate and thus a **decreased bicarbonate level**, and an **increased anion gap**.
*↑ pH, ↑ bicarbonate, and normal pCO2*
- This pattern suggests a **metabolic alkalosis**, which is inconsistent with the patient's presentation of DKA.
- Metabolic alkalosis is typically seen in conditions like severe vomiting or diuretic use, not uncontrolled diabetes.
*↑ pH, normal bicarbonate and ↓ pCO2*
- This profile describes **respiratory alkalosis**, often caused by primary hyperventilation.
- While the patient has rapid and deep breathing (Kussmaul respiration), this is a compensatory mechanism for metabolic acidosis, not a primary respiratory alkalosis.
*↓ pH, ↓ bicarbonate and normal anion gap*
- This indicates a **normal anion gap metabolic acidosis**, also known as hyperchloremic acidosis.
- This is typically seen in conditions like renal tubular acidosis or severe diarrhea, where bicarbonate is lost or chloride is retained, which is not the case for DKA.
*↓ pH, normal bicarbonate and ↑ pCO2*
- This presentation indicates **respiratory acidosis**, which is caused by hypoventilation and retention of CO2.
- The patient's rapid and deep breathing (Kussmaul breathing) is a compensatory mechanism to blow off CO2 and would decrease pCO2, not increase it.
Ketone body metabolism US Medical PG Question 10: A scientist is trying to design a drug to modulate cellular metabolism in the treatment of obesity. Specifically, he is interested in understanding how fats are processed in adipocytes in response to different energy states. His target is a protein within these cells that catalyzes catabolism of an energy source. The products of this reaction are subsequently used in gluconeogenesis or β-oxidation. Which of the following is true of the most likely protein that is being studied by this scientist?
- A. It is stimulated by epinephrine (Correct Answer)
- B. It is inhibited by glucagon
- C. It is inhibited by acetylcholine
- D. It is inhibited by cortisol
- E. It is stimulated by insulin
Ketone body metabolism Explanation: ***It is stimulated by epinephrine***
- The protein described is likely **hormone-sensitive lipase (HSL)**, which catabolizes **triglycerides** in adipocytes to **glycerol** and **fatty acids**.
- **Epinephrine** (and norepinephrine) stimulates HSL activity via a **cAMP-dependent protein kinase A (PKA)** pathway, leading to increased fatty acid release for energy.
*It is inhibited by glucagon*
- **Glucagon primarily acts on the liver** to promote gluconeogenesis and glycogenolysis, but it does **not directly inhibit HSL** in adipocytes.
- While glucagon has a lipolytic effect, it doesn't inhibit the enzyme that releases fatty acids.
*It is inhibited by acetylcholine*
- **Acetylcholine** is a neurotransmitter involved in the **parasympathetic nervous system**, which generally promotes energy storage.
- It does **not directly inhibit HSL**; its effects on lipid metabolism are indirect and typically involve other pathways.
*It is inhibited by cortisol*
- **Cortisol**, a glucocorticoid, generally **promotes lipolysis** (breakdown of fats) in certain contexts, particularly during stress to provide energy substrates.
- Therefore, it would **not inhibit HSL**; rather, it often enhances its activity or provides a permissive effect for other lipolytic hormones.
*It is stimulated by insulin*
- **Insulin** is an **anabolic hormone** that promotes energy storage, including **lipogenesis** (fat synthesis) and inhibits lipolysis.
- Insulin **inhibits HSL activity** by activating phosphodiesterase, which reduces cAMP levels, thus deactivating PKA and preventing HSL phosphorylation.
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